Background: Seminal vesicle protein number 4 (SV-IV) is a small, basic, multifunctional, intrinsically disordered secretory protein synthesized in large amounts by rat seminal vesicle epithelium under androgen transcriptional control. SV-IV-immunorelated proteins occur in other rat tissues and in humans. Methods: The in vitro effect of SV-IV on human FcΕRI+ cells was investigated by standard immunologic, biochemical and molecular biology procedures. Results: SV-IV-induced histamine release from human basophils and lung mast cells without any influence on leukotriene C4 release and cell migration. The histamine release rate was slower compared with that induced by anti-IgE, the temperature dependence of the event being similar. SV-IV-induced histamine release was Ca2+-dependent, suggesting a physiological interaction of the protein with FcΕRI+ cells. SV-IV and anti-IgE acted synergistically on the histamine release. SV-IV did not induce de novo synthesis of cytokines and growth factors (transforming growth factor-β1, interleukin-10, interleukin-13, tumor necrosis factor-α, vascular endothelial growth factor A) in FcΕRI+ cells. Conclusions: SV-IV protein induces in human FcΕRI+ cells the release of histamine, a proinflammatory, antiapoptotic and immunosuppressive biogenic amine. These data: (1) are consistent with the antiapoptotic and immunosuppressive properties of SV-IV; (2) confirm a regulatory feature of SV-IV on mammal inflammatory reactivity by either inhibiting the arachidonate cascade pathway or stimulating proinflammatory cytokine release from lymphocyte/monocytes and histamine from FcΕRI+ cells; (3) raise the possibility of a protective role of SV-IV on implanting hemiallogenic blastocysts against maternal reactive oxygen species and immunological attacks at the uterine implantation site.

Keywords:
Protein SV-IV, Mast cells, Basophils, FcεRI receptor, Histamine, Degranulation, Blastocyst implantation
1.
Ostrowski MC, Kistler MK, Kistler WS: Purification and cell-free synthesis of a major protein from rat seminal vesicle secretion. A potential marker for androgen action. J Biol Chem 1979;254:383–390.
2.
Pan YC, Li SSL: Structure of secretory protein IV from rat seminal vesicles. Int J Pept Protein Res 1982;20:177–187.
3.
Mansson PE, Sugino A, Harris SE: Use of a cloned-double stranded cDNA coding for a major androgen-dependent protein in rat seminal vesicle secretion: the effect of testosterone in gene expression. Nucleic Acids Res 1981;9:935–946.
4.
Stiuso P, Metafora S, Facchiano AM, Colonna G, Ragone R: The self-association of protein SV-IV and its possible functional implications. Eur J Biochem 1999;266:1029–1035.
5.
Caporale C, Caruso C, Colonna G, Facchiano A, Ferranti P, Mamone G, Picariello G, Colonna F, Metafora S, Stiuso P: Structural properties of the protein SV-IV. Eur J Biochem 2004;271:263–271.
6.
Harris SE, Mansson PE, Tully DB, Burkhart B: Seminal vesicle secretion IV gene: allelic difference due to a series of 20-base-pair direct tandem repeats within an intron. Proc Natl Acad Sci USA 1983;80:6460–6464.
7.
Kandala C, Kistler MK, Lawther RP, Kistler WS: Characterization of a genomic clone for rat seminal vesicle secretory protein IV. Nucleic Acids Res 1983;11:3169–3186.
8.
McDonald C, Williams L, McTurck P, Fuller F, McIntosh E, Higgins S: Isolation and characterisation of genes for androgen-responsive secretory proteins of rat seminal vesicles. Nucleic Acids Res 1983;11:917–930.
9.
D’Ambrosio E, Del Grosso N, Ravagnan G, Peluso G, Metafora S: Cloning and expression of the rat genomic DNA sequence coding for the secreted form of the protein SV-IV. Bull Mol Biol Med 1993;18:215–223.
10.
Vilasi S, Ragone R: Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicle. FEBS J 2008;275:763–774.
11.
Stiuso P, Metafora S, Facchiano AM, Colonna G, Ragone R: The self-association of protein SV-IV and its possible functional implications. Eur J Biochem 1999;266:1029–1035.
12.
Caporale C, Caruso C, Colonna G, Facchiano A, Ferranti P, Mamone G, Picariello G, Colonna F, Metafora S, Stiuso P: Structural properties of the protein SV-IV. Eur J Biochem 2004;271:263–271.
13.
Tufano MA, Porta R, Farzati B, Di Pierro P, Rossano F, Catalanotti P, Baroni A, Metafora S: Rat seminal vesicle protein SV-IV and its transglutaminase-synthesized polyaminated derivative Spd2-SV-IV induce cytokine release from human resting lymphocytes and monocytes in vitro. Cell Immunol 1996;168:148–157.
14.
Abrescia P, Lombardi G, De Rosa M, Quagliozzi L, Guardiola J, Metafora S: Identification and preliminary characterization of a sperm-binding protein in normal human semen. J Reprod Fertil 1985;73:71–77.
15.
Metafora S, Facchiano F, Facchiano A, Esposito C, Peluso G, Porta R: Homology between rabbit uteroglobin and the rat seminal vesicle sperm binding protein: prediction of structural features of glutamine substrates for transglutaminase. J Prot Chem 1987;6:353–359.
16.
Metafora S, Lombardi G, De Rosa M, Quagliozzi L, Ravagnan G, Peluso G, Abrescia P: Protein family immunorelated to a sperm-binding protein and its regulation in human semen. Gamete Res 1987;16:229–241.
17.
Morelli F, Peluso G, Petillo O, Giannattasio A, Filosa S, Motta CM, Tammaro S, Zatterale A, Calzone R, Budillon A, Carteni M, De Maria S, Costanza MR, Nigro A, Petrazzuolo M, Buommino E, Rizzo M, Capasso G, Baiano S, Moscatiello F, Ravagnan G, Fuggetta MP, Tajana G, Stiuso P, Metafora BM, Metafora V, Metafora S: The immunomodulatory protein SV-IV protects serum-deprived cells against apoptosis but not against G0/G1 arrest: possible implications for the survival of implanting embryo. J Cell Physiol 2007;212:610–625.
18.
Galdiero F, Tufano MA, De Martino L, Capasso C, Porta R, Ravagnan G, Peluso G, Metafora S: Inhibition of macrophage phagocytic activity by SV-IV, a major protein secreted from the rat seminal vesicle epithelium. J Reprod Immunol 1989;16:269–284.
19.
Metafora S, Peluso G, Persico P, Ravagnan G, Esposito C, Porta R: Immunosuppressive and anti-inflammatory properties of a major protein secreted from the epithelium of the rat seminal vesicles. Biochem Pharmacol 1989;38:121–131.
20.
Metafora S, Porta R, Ravagnan G, Peluso G, Tufano MA, De Martino L, Ianniello R, Galdiero F: Inhibitory effect of SV-IV, a major protein secreted from the rat seminal vesicle epithelium, on phagocytosis and chemotaxis of human polymorphonuclear leukocytes. J Leukoc Biol 1989;46:409–416.
21.
Camussi G, Tetta C, Bussolino F, Metafora S, Peluso G, Esposito C, Porta R: An anti-inflammatory protein secreted from the rat seminal vesicle epithelium inhibits the synthesis of platelet-activating factor and the release of arachidonic acid and prostacyclin. Eur J Biochem 1990;192:481–485.
22.
Vuotto ML, Peluso G, Mancino D, Colonna G, Facchiano A, Ielpo MT, Ravagnan G, Metafora S: Inhibition of interleukin-1 release and activity by the rat seminal vesicle protein SV-IV. J Leukoc Biol 1993;5:3214–3222.
23.
Peluso G, Porta R, Esposito C, Tufano MA, Toraldo R, Vuotto ML, Ravagnan G, Metafora S: Suppression of rat epididymal sperm immunogenicity by a seminal vesicle secretory protein and transglutaminase both in vivo and in vitro. Biol Reprod 1994;50:593–602.
24.
Romano-Carratelli C, Bentivoglio C, Nuzzo I, Benedetto N, Buommino E, Cozzolino A, Cartenı‘ M, Morelli F, Costanza MR, Metafora B, Metafora V, Metafora S: Effect of protein SV-IV on experimental Salmonella enterica serovar typhimurium infection in mice. Clin Diagn Lab Immunol 2002;9:115–125.
25.
Metafora V, Franco P, Massa O, Morelli F, Stiuso P, Ferranti P, Mamone G, Malorni A, Stoppelli MP, Metafora S: Phosphorylation of seminal vesicle protein IV on Ser58 enhances its peroxidase-stimulating activity. Eur J Biochem 2001;268:3858–3869.
26.
Metafora V, Stiuso P, Ferranti P, Giannattasio A, Dicitore A, Ravagnan G, De Maria S, Pontoni G, Cartenì M, Metafora S: In vitro stimulatory effect of anti-apoptotic seminal vesicle protein 4 on purified peroxidase enzymes. FEBS J 2008;275:3870–3883.
27.
Romano-Carratelli C, Galdiero M, Nuzzo I, Bentivoglio C, Porta R, Peluso G, Ravagnan G, Metafora S: In vivo inhibition of cell-mediated and humoral immune responses to cellular antigens by SV-IV, a major protein secreted from the rat seminal vesicle epithelium. J Reprod Immunol 1995;28:15–30.
28.
Fuggetta MP, Lanzilli G, Cottarelli A, Ravagnan G, Cartenì M, De Maria S, Metafora BM, Metafora V, Metafora S: Anti-apoptotic seminal vesicle protein IV inhibits cell-mediated immunity. J Reprod Immunol 2008;78:85–93.
29.
Marone G, Triggiani M, Genovese A, de Paulis A: Role of human mast cells and basophils in bronchial asthma. Adv Immunol 2005;88:97–160.
30.
Galli SJ, Nakae S, Tsai M: Mast cells in the development of adaptive immune responses. Nat Immunol 2005;6:135–142.
31.
Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M: Mast cells as ‘tunable’ effector and immunoregulatory cells: recent advances. Annu Rev Immunol 2005;23:749–786.
32.
Ryan JJ, Kashyap M, Bailey D, Kennedy S, Speiran K, Brenzovich J, Barnstein B, Oskeritzian C, Gomez G: Mast cell homeostasis: a fundamental aspect of allergic disease. Crit Rev Immunol 2007;27:15–32.
33.
Metcalfe DD, Baram D, Mekori YA: Mast cells. Physiol Rev 1997;77:1033–1079.
34.
Marone G, Triggiani M, de Paulis A: Mast cells and basophils: friends as well as foes in bronchial asthma? Trends Immunol 2005;26:25–31.
35.
de Paulis A, Prevete N, Fiorentino I, Walls AF, Curto M, Petraroli A, Castaldo V, Ceppa P, Fiocca R, Marone G: Basophils infiltrate human gastric mucosa at sites of Helicobacter pylori infection, and exhibit chemotaxis in response to H. pylori-derived peptide Hp(2–20). J Immunol 2004;172:7734–7743.
36.
MacGlashan D Jr: Histamine: a mediator of inflammation. J Allergy Clin Immunol 2003;112:S53–S59.
37.
Mellqvist UH, Hansson M, Brune M, Dahlgren C, Hermodsson S, Hellstrand K: Natural killer cell dysfunction and apoptosis induced by chronic myelogenous leukemia cells: role of reactive oxygen species and regulation by histamine. Blood 2000;96:1961–1968.
38.
Hansson M, Hermodsson S, Brune M, Mellqvist UH, Naredi P, Betten A, Gehlsen KR, Hellstrand K: Histamine protects T cells and natural killer cells against oxidative stress. J Interferon Cytokine Res 1999;19:1135–1144.
39.
Cocchiara R, Di Trapani G, Azzolina A, Albeggiani G, Geraci D: Early embryonic histamine-releasing factor: a new model for human implantation. Hum Reprod 1986;1:445–447.
40.
Beer DJ, Rocklin RE: Histamine-induced suppressor-cell activity. J Allergy Clin Immunol 1984;73:439–452.
41.
Beer DJ, Matloff SM, Rocklin RE: The influence of histamine on immune and inflammatory responses. Adv Immunol 1984;35:209–268.
42.
de Paulis A, De Palma R, Di Gioia L, Carfora M, Prevete N, Tosi G, Accolla RS, Marone G: Tat protein is an HIV-1-encoded β-chemokine homolog that promotes migration and up-regulates CCR3 expression on human Fc epsilon RI+ cells. J Immunol 2000;165:7171–7179.
43.
Porta R, Esposito C, Metafora S, Malorni A, Pucci P, Siciliano R, Marino G: Mass spectrometric identification of the amino donor and acceptor sites in a transglutaminase protein substrate secreted from rat seminal vesicles. Biochemistry 1991;30:3114–3120.
44.
Yin ET, Galanos C, Kinsky S, Bradshaw RA, Wessler S, Luderig O, Sarmiento MF: Picogram-sensitive assay for endotoxin: gelation of Limulus polyphemus blood cell lysate induced by purified lipopolysaccharides and lipid A from Gram-negative bacteria. Biochim Biophys Acta 1972;261:284–289.
45.
Rubin BY, Anderson SL, Sullivan SA, Williamson BD, Carswell EA, Old L: Purification and characterization of a human tumor necrosis factor from the LuKII cell line. Proc Natl Acad Sci USA 1985;82:6637–6641.
46.
Ma Y, Zeng S, Metcalfe DD, Akin C, Dimitrijevic S, Butterfield JH, McMahon G, Longley BJ: The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood 2002;99:1741–1744.
47.
Florio G, Petraroli A, Patella V, Triggiani M, Marone G: The immunoglobulin superantigen-binding site of HIV-1 gp120 activates human basophils. AIDS 2000;14:931–938.
48.
de Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, Ragno P, Longobardi A, Liccardo B, Genovese A, Ribatti D, Walls AF, Marone G: Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol 2006;177:7322–7331.
49.
Nagao M, Hiraguchi Y, Hosoki K, Tokuda R, Usui T, Masuda S, Yamaguchi M, Fujisawa T: Allergen-induced basophil CD203c expression as a biomarker for rush immunotherapy in patients with Japanese cedar pollinosis. Int Arch Allergy Immunol 2008;146(suppl 1):47–53.
50.
Malbrán A, Yeyati E, Rey GL, Galassi N: Diclofenac induces basophil degranulation without increasing CD63 expression in sensitive patients. Clin Exp Immunol 2007;147:99–105.
51.
Dahinden CA, Kurimoto J, Baggiolini M, Dewald B, Walz A: Histamine and sulfidoleukotriene release from human basophils: different effects of antigen, anti-IgE, C5a, f-Met-Leu-Phe and the novel neutrophil-activating peptide NAF. Int Arch Allergy Appl Immunol 1989;90:113–118.
52.
Schleimer RP, Gillespie E, Lichtenstein LM: Release of histamine from human leukocytes stimulated with the tumor-promoting phorbol diesters. I. Characterization of the response. J Immunol 1981;126:570–574.
53.
Genovese A, Stellato C, Patella V, Lamparter-Schummert B, de Crescenzo G, Adt M, Marone G: Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung, but not skin tissue. Int J Clin Lab Res 1996;26:192–198.
54.
Patella V, Ciccarelli A, Lamparter-Schummert B, de Paulis A, Adt M, Marone G: Heterogeneous effects of protamine on human mast cells and basophils. Br J Anaesth 1997;78:724–730.
55.
Paonessa G, Metafora S, Tajana G, Abrescia P, De Santis A, Gentile V, Porta R: Transglutaminase-mediated modifications of the rat sperm surface in vitro. Science 1984;226:852–855.
56.
Manco G, Abrescia P: A major secretory protein from rat seminal vesicle binds ejaculated spermatozoa. Gamete Res 1988;21:71–84.
57.
Guerin P, El Mouatassim S, Menezo Y: Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 2001;7:175–189.
58.
Cocchiara R, Di Trapani G, Azzolina A, Albeggiani G, Ciriminna R, Cefalu E, Cittadini E, Geraci D: Isolation of a histamine releasing factor from human embryo culture medium after in-vitro fertilization. Hum Reprod 1987;2:341–344.
59.
Cocchiara R, Albeggiani G, Di Trapani G, Azzolina A, Lampiasi N, Cervello G, Geraci D: Dispersal of rat uterine mast cells and their functional response to an embryo-derived histamine releasing factor: a possible model for embryo implantation. J Reprod Immunol 1988;14:191–201.
60.
Cocchiara R, Lampiasi N, Albeggiani G, Azzolina A, Bongiovanni A, Gianaroli L, Di Blasi F, Geraci D: A factor secreted by human embryo stimulates cytokine release by uterine mast cell. Mol Hum Reprod 1996;2:781–791.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.